Associations between Sex Hormones and Circulating Growth Differentiation Factor-15 in Male Patients with Major Depressive Disorder

Sun, Ting; Peng, Rui; Sun, X. F.; Li, Yan

doi:10.3390/brainsci11121612

Cited by 6 publications

(6 citation statements)

References 41 publications

(47 reference statements)

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“…This is in accordance with the previous finding that older male patients had higher GDF15 levels than female patients [35]. Although underlying mechanisms are not clear so far, this might be explained by sex hormone effects on GDF15 [36].…”

Section: Discussionsupporting

confidence: 93%

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

Kochlik,

Herpich,

Moreno-Villanueva

et al. 2023

GeroScience

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Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE (“European study to establish bioMARKers of human AGEing“) participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted β = 0.177 [0.044 – 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 – 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 – 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults.

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Section: Discussionsupporting

confidence: 93%

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

Kochlik,

Herpich,

Moreno-Villanueva

et al. 2023

GeroScience

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“…Furthermore, Schwarz et al 53 identified a subgroup of schizophrenia patients with hormonal abnormalities, including increased testosterone. It has been hypothesized that testosterone might be protective because of its anti-inflammatory properties, 54 aligning with the growing recognition of inflammation in mental illness. 55 Our MVMR analysis confirmed the anti-inflammatory effect of testosterone, as CRP's effect decreased.…”

Section: Discussionmentioning

confidence: 99%

The role of sex hormones in severe mental illness: a genetic exploration

Veeneman,

Verweij,

Sommer

et al. 2024

Preprint

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IntroductionDespite advances in psychotherapies and pharmacological treatments, the burden of severe mental illness (SMI) remains high. Prominent sex differences exist in SMI, with increasing evidence pointing towards a pivotal role for sex hormones. Elucidation of these hormonal influences is crucial to tailor sex-specific prevention and treatment.MethodsTo investigate potential shared genetics and bi-directional causal effects between sex hormone traits and SMI, we computed genetic correlations using linkage disequilibrium score regression and bi-directional summary-level Mendelian Randomization (MR). A range of sensitivity methods was applied and potential mediators were investigated using multivariable MR. Sex-stratified data from genome-wide association studies (GWAS)s were used, further stratified on menopausal status when available. The main analysis focused on depressive disorder (N women=23,618 and N men=17,336), bipolar disorder (N women=26,573 and N men=22,381), schizophrenia (N women=54,513 and N men=68,287) as SMIs, and oestrogen (N women=229,966 and N men=206,927) and testosterone (N women=230,454 and N men=194,453) as the primary sex hormone traits. Exploratory analyses included other sex hormone traits (progesterone, sex hormone-binding globulin, prolactin, age of menarche, age of menopause). Potential mediators examined included levels of cortisol and CRP, smoking initiation, alcohol dependence, alcohol intake, BMI and body fat distribution. Only individuals of European ancestry were included.ResultsWe found a widespread pattern of significant genetic correlations between oestrogen/testosterone levels and depressive disorder/schizophrenia, in both positive and negative directions in both sexes (ranging between -0.22 and 0.13). There was no significant genetic correlation for bipolar disorder. In the MR analyses, evidence for causal effects was largely lacking; however, there was consistent evidence for a causal, increasing effect of testosterone levels on schizophrenia risk in men, completely mediated by CRP. Conversely, there was evidence for a causal, increasing effect of liability to schizophrenia on testosterone levels in both sexes.ConclusionThis study offers new insights into the complex aetiology of SMI by comprehensively mapping genetic associations with sex hormone traits, emphasizing the need to further investigate sex hormones’ impact on SMI using larger and more precisely phenotyped samples to identify individuals particularly vulnerable to hormonal disturbances.

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“…These findings suggest that androgen may be associated with GDF‐15 expression 20–22 . In addition, studies have linked the increased expression of GDF‐15 with testosterone deficiency in men with coronary artery disease, and shown a correlation between high GDF‐15 levels and low testosterone in other diseases such as depression 23,24 . However, there are currently no reports on the relationship between GDF‐15 and testosterone deficiency in men with T2DM.…”

Section: Introductionmentioning

confidence: 97%

“…[20][21][22] In addition, studies have linked the increased expression of GDF-15 with testosterone deficiency in men with coronary artery disease, and shown a correlation between high GDF-15 levels and low testosterone in other diseases such as depression. 23,24 However, there are currently no reports on the relationship between GDF-15 and testosterone deficiency in men with T2DM. This study therefore investigated male patients with T2DM to examine the relationship between high levels of GDF-15 and testosterone deficiency.…”

Section: Introductionmentioning

confidence: 99%

Raised circulating soluble growth differentiation factor 15 is negatively associated with testosterone level in hypogonadic men with type 2 diabetes

Mei

Lyu

et al. 2022

Diabetes Metabolism Res

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Aims Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor‐15 (GDF‐15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF‐15 levels and hypogonadism in Chinese male patients with T2DM. Materials and Methods A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF‐15 and total testosterone concentrations were quantified by an enzyme‐linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF‐15 levels and hypogonadism in these patients. Results When compared with T2DM patients without hypogonadism circulating GDF‐15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p < 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p < 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF‐15 and testosterone deficiency were −1.795 (−2.929, −0.661). Serum GDF‐15 levels were also associated positively with testosterone deficiency in each logistic regression model (p < 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p < 0.01). Conclusions In hypogonadal men with T2DM, an elevated serum GDF‐15 level is associated negatively with serum testosterone concentration. GDF‐15 may be a novel cytokine related to T2DM men with hypogonadism.

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Associations between Sex Hormones and Circulating Growth Differentiation Factor-15 in Male Patients with Major Depressive Disorder

Cited by 6 publications

References 41 publications

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

The role of sex hormones in severe mental illness: a genetic exploration

Raised circulating soluble growth differentiation factor 15 is negatively associated with testosterone level in hypogonadic men with type 2 diabetes

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